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Biomed > biomed week 8 > Flashcards

biomed week 8 Flashcards

1
Q

light microscopy can visualize structures as small as

A

0.2 microns

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2
Q

what are the two different types of microscopes

A

fluorescence and confocal

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3
Q

confocal microscopy can view

A

cell or tissue in a particular plane

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4
Q

electron microscopy can visualize structures as small as ….. the tissue are often ….. in …….. …….

A

3nm
frozen, liquid nitrogen

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5
Q

tissues and cells viewed in microscopes are always

A

dead

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6
Q

what is fixation?

A

chemicals cross-link proteins and inactivate
enzymes that degrade cells/cellular components

However, chemical characteristics of molecules are
mostly retained so that staining the tissue still occurs

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7
Q

what is Dehydration & clearing

A

tissues are passed through alcohol
solutions (replaces the water) and then the alcohol is
removed

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8
Q

what is Infiltration and embedding

A

the tissue is infiltrated with a
substance (i.e. paraffin wax) and then allowed to harden

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9
Q

what is Trimming in histology

A

tissue is sliced into thin, almost transparent
slices using a microtome

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10
Q

what is Hematoxylin and eosin

A

usually both done together in a
tissue preparation

Hematoxylin is a dark blue basic dye, and will bind to negatively-charged molecules
- Molecules that bind to basic dyes are known as
basophilic molecules

Eosin is a pink acidic dye – it binds to positively-charged molecules (i.e. cytosolic proteins)
- Eosin is acidophilic

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11
Q

Periodic acid-Schiff stain is great at showing what?

A

glycogen and many glycoproteins

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12
Q

what cell/ organelle is hematoxylin highlighted in

A

nucleus

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13
Q

what cell/organelle is eosin highlighted in

A

nucleus

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14
Q

what organelle/ cell is PAS highlighted in

A

cytosol, mucous some ECM

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15
Q

what is the trichrome stain? what organelle cell is highlighted?

A

Keratin, collagen, DNA, cytoplasmic proteins

Muscle fibres, nuclei, collagen –complicated stain

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16
Q

why is histology useful?

A

At the junction of anatomy and physiology

Much of the function of a cell or tissue can be deduced by its microscopic structure

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17
Q

where are simple squamous cells found

A

air sacs of lungs, lining of the heart, blood vessels and lymphatic vessles,
allows materials to pass through with diffusion (exchange epithelium

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18
Q

simple cubodial epithilium cells are found where

A

in ducts and secretory portions of small glands in the kidney tubules

function: secretes and absorbs, transport epitilium

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19
Q

simple columbar epithelium where is it found?

A

microvilli in the GI tract

secretes mucous and enzymes
- increases surface area and absorption

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20
Q

pesudostratified columnar epithelium function and location

A

cilliated tissue that lines the brochii, trachea and much of the upper respiratory tract

secretes mucous

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21
Q

stratified squamous epithelium function and location

A

lines the esophagus, vagina and mouth

skin

protects against abrasion

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22
Q

transitional epithelium function and location

A

lines the bladder, urethra, urinary tract

allows them to expand and stretch
- chemical protection from urine

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23
Q

what is paracellular movement

A

between epithelial cells, movement across junctions

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24
Q

what is transcellular movement

A

through epithelial cells, movement across apical and basolateral cell membranes

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25
Q

flat cell is called

A

squamous

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26
Q

a square cell is called

A

cuboidal

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27
Q

a tall cell is called

A

columbar

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28
Q

only one layer of cells is called

A

simple

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29
Q

what are multiple layered cells called

A

stratified

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30
Q

Stratified epithelia (i.e. skin) is named based on the shape of the

A

cell farthest from the base

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31
Q

even though there are cuboidal cells at the base of the epidermis, the cells at the “top” are flattened therefore it is called ….

A

stratified squamous epithelium

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32
Q

If there are cilia…

A

then it’s a ciliated epithelium

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33
Q

Actin filaments are for

A

shape and motility of
the cell

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34
Q

Intermediate filaments do what for the cell

A

structural
“strength” to the cell
* Desmin, keratin

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35
Q

Microtubules determine ….

A

polarity, cell division, movement of cilia (if
present)

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36
Q

what are tight junctions

A

Located at the apical aspect
of almost all epithelial cells

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37
Q

where are tight junctions found

A

Found in the gut, brain,
skin, respiratory tract
§ Closest to the lumen of
all the junctions

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38
Q

what are the key functions of tight junctions

A

Barrier that prevents movement of undesirable
substances to the tissues below

Regulates the movement of a variety of molecules
between cells, through the barrier

Helps establish polarity – TJs seem to help direct membrane proteins to the apical vs. basolateral sides

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39
Q

what are the key proteins in tight junctions

A

Claudins – trans-membrane proteins that can act as channels
- for small molecules (paracellular)
- Some are permeable (Claudin2), some are relatively
impermeable (Claudin-1)

Occludin – trans-membrane protein, function not clear

Junctional adhesion molecules (JAM)
- Trans-membrane protein that may
mediate permeability to larger molecules

ZO-proteins
- Important in tight junction formation,
interact with the cytoskeleton

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40
Q

what is the structure of tight junctions

A
  • Claudins and JAMs are transmembrane proteins
  • extend into the extracellular space
    and bind to claudins and JAMs on the
    neighbouring cells
  • ZO proteins bind to the intracellular face
    of claudins and JAMs, linking them to
    the actin cytoskeleton underneath
  • Cell membrane proteins, even lipids
    seem unable to cross the “belt” of the
    TJs
    - Keeps basolateral and apical cell
    membrane components separated
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41
Q

where are adherens junctions typically found

A

Found immediately below tight junctions

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42
Q

what is the function of adheres junctions

A
  • Strengthens and
    stabilizes tight junctions
  • Participates in cell-cell
    signaling that regulates
    cell division and
    proliferation
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43
Q

what are the key proteins in adheres junctions

A

Cadherin – transmembrane protein that
interacts with other cadherins on the
neighbouring cell (similar to claudins)

Catenins – linker molecules that connect the
intracellular face of claudins to the actin
cytoskeleton

     - Beta catenin can also act as a signal
     - When cadherins connect across cells,
            beta-catenin remains associated with
              cadherins
     - When they don’t connect, beta-catenin
           can dissociate and signal cell division
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44
Q

how might adherens junctions (beta catenin) regulate wound healing?

A

send signals that we need more catherin to be made to bridge gap between epithelial cells

when there is an injury, the cll might die off, the connection will be lost, if lost beta catenin will signal that we need more proteins and cell division

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45
Q

epithelial cells have blood vessels

A

false, they are avascular

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46
Q

adherns junctions and tight junctions circle ……

A

the entire apical aspect of a colunar of cuboidal cells

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47
Q

desmosomes only attach to ….

A

certain spots on the epithelial cell membrane

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48
Q

what are the key similarities of desmosomes versus adheres junctions

A
  • Strong adhesion between cells
  • Desmosomes use cadherin-like
    molecules
  • Both have intracellular
    “plaques” that interact with
    proteins that can act as
    “signalers” and “linkers” (i.e.
    beta-catenin)
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49
Q

what are the key differences between desmosomes and adheres junctions

A
  • Desmosomes connect to
    intracellular intermediate
    filaments (i.e. keratin)
  • Desmosomes provide more
    structural stability to the cell
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50
Q

what are significant differences between desmosomes and hemidesmosomes

A
  • Transmembrane “linking” protein is an integrin, not a claudin-like molecule
  • Integrin binds to a component of the basement membrane known as laminin
    -Does not bind to a molecule on an adjacent cell
  • Hemidesmosomes do not seem to have important intracellular signaling functions
  • Hemidesmosomes do link to intracellular intermediate filaments
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51
Q

what is the function of hemidesmosomes

A

adhesion of the epithelial cell to the basement membrane

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52
Q

barrier that restricts movement of substances apical to basal

A

tight junctions

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53
Q

Transport of substances from the apical side to the basal side of the epithelium is what type of junction?

A

tight junctions, claudins

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54
Q

strength of the epithelial lining

A

adherens , desmosomes

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55
Q

Determination of polarity (apical vs. basal) across the
epithelial cell

A

tight junction

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56
Q

Signaling and regulation of the activity of the epithelial cell

A

adheres, gap junctions

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57
Q

Anchoring the epithelial cell to the underlying connective tissue

A

hemidesmosomes

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58
Q

cillia have a …….. structure of microtubules , with a central doublet

A

9+2

  • Bound to a basal body-like structure
    at the apex of the membrane – also
    composed of microtubules
    (axoneme)
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59
Q

Almost all cells – including epithelial cells - have one primary cilia These are non-motile cilia that have a

A

ring of 9
microtubular structures, but no central doublet

Very long – range from 1 – 10 microns (much longer
than microvilli)

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60
Q

The primary cilia have a range of receptors and intracellular signaling mechanisms that communicate information from the external environment to the cell
why is this important?

A

Extremely important in development of the embryo,
sensing fluid movements, and sensing the presence of
growth factors

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61
Q

loose connective tissue is usually found

A

often found beneath the epithelial lining of many tissues
- Lamina propria of the intestine,
respiratory tract
- Can also be found as “packing” between
muscle fibres, within nerves, etc.
Lots of ground substance, many cells, relatively little
collagen

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62
Q

Dense irregular connective tissue has ………….

A

Fewer cells, less ground substance than loose connective tissue

Much more collagen
- Collagen is arrayed in bundles
that are not parallel, but
arranged in many different
directions
- Resists stresses from multiple
different directions

Found in capsules that surround organs and in the dermis

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63
Q

Dense regular connective tissue consists of

A
  • Lots of collagen (type I) with less ground
    substance and cells than loose connective
    tissue
  • Collagen is oriented in one particular
    direction
  • Resists stresses along one line or plane
  • Typical examples – tendons, ligaments,
    aponeuroses
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64
Q

Collagen consisits of

A

fibroblasts

  • Different types of collagen have
    different functions

Type 1 – resists tension, multiple
triple helices bound together to
form fibrils, and fibrils are
organized to form fibres

-Major collagen type in dense CT
and bone

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65
Q

Type II collagen is

A

smaller fibrils with less organized orientation
than dense regular tissue

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66
Q

type 3 collagen is

A

reticular fibres
§ Major component of loose connective tissue

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67
Q

Type I, II, and III collagens are known as

A

fibrillar collagens

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68
Q

Type IV collagen – forms the basement membrane that connects

A

epithelial and connective tissue layers

  • Forms a sort of cross-linked “net” with laminin
    (glycoprotein) and proteoglycans interspersed within it
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69
Q

Type IV Collagen in the Basement Membrane

A

The basement membrane is formed from an organized meshwork of type IV collagen, proteoglycans, and laminin

Note that integrins (hemidesmosomes) bind to the
laminin in the basement membrane

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70
Q

Connective Tissue Proper – Ground
Substance
Two major components:

A

Multi-adhesive glycoproteins
Proteoglycans

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71
Q

Multi-adhesive glycoproteins bind to

A

a wide variety of components of the extracellular matrix

ex
- laminin binds to type IV collagen and the integrins of hemidesmosomes

  • Fibronectin binds to collagen, glycosaminoglycans (GAGs) on proteoglycans, and some integrins
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72
Q

describe the Proteoglycans – 3-part structure:

A
  • A very long, linear polymer of hyaluronic acid (a GAG)
  • Linking proteins attached to the hyaluronic acid polymer
  • Shorter GAG chains attached to the linking proteins
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73
Q

Proteoglycans are highly …………..

An ECM rich in proteoglycans is
difficult for ………

proteoglycans store ……..

A

hydrated “collect” water in
the ECM due to the OH-groups on
the carbohydrate GAGs

most bacteria to penetrate

“Store” of growth factors
- Messengers can be “stored”
within the ECM – associated
with proteoglycans
– When the ECM is broken
down, these factors are
liberated à replacement of
the ECM

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74
Q

what are some common pathology sources of the epithelium

A

-Disrupted barrier or protective function of the epithelial lining
- Disrupted transport across the epithelial lining
-Inflammation in the connective tissue below the epithelium
* Due to autoimmune or allergic conditions
* Due to infection
- Malignant transformation of epithelial cells

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75
Q

what epithelial tissue is the skin made up of

A

Stratified squamous epithelium

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76
Q

what are the typical functions of stratified squamous epithelium

A

protection against abrasion, they are dead in the coreum

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77
Q

Apical layers – cells that accumulate
keratin, “compact” it, and eventually

A

die

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78
Q

Keratin = main intermediate filament in

A

keratinocytes

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79
Q

Keratin is strong and forms bundles –

A

a barrier that prevents water loss from
deeper layers and microbe invasion

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80
Q

keratin complexes with another protein called

A

filaggrin

– that helps compact keratin
and attracts water, aiding in skin
moisturization

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81
Q

as skin matures from deeper layers …… which causes ……… what is the net result?

A

junctions are modified

  • Loss of hemidesmosomes (no contact with the basement membrane)
  • Modification of desmosomes
  • Tight junctions remain

Net result – the “outside” surface
of the skin is flattened layers of
dead “bags” of keratin and
filaggrin linked by tight junctions

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82
Q

what is the dermal layer

A
  • Dense irregular connective tissue
    -Capillary loops extend from the papillary dermis, bringing nutrients and exchanging gases and wastes
  • Dermal vasculature allows immune cells to enter the
    epidermis
    - Fight infection
    - Heal wounds
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83
Q

what is Atopic dermatitis

A

One of the most common skin conditions

Typical symptoms & signs:
§ Itchy papules and plaques that can
become excoriated with scratching
§ Distributed over the extensor
surfaces, face, and scalp
§ Worsen in response to allergen
exposure

Highly heritable – children of parents with atopic dermatitis have
§ Subtle abnormalities in filaggrin impair the ability of the more
apical strata to retain the moisture of the skin
§ Tight junction changes to more permeable types decrease the
barrier function of the skin

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84
Q

Postulated sequence of events of atopic dermatitis

A

Impaired skin barrier -> repeated introduction of antigens to immune cells that reside in the epidermis and the dermis ->
recruitment of other, particular immune cells into the dermis and epidermis from the blood stream -> a specific type of inflammation (type 2) that causes excessive histamine release into the skin -> chronic swelling and itch with further antigen
exposure

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85
Q

The Intestinal Mucosa –
General Structure

A

Simple columnar epithelium – prominent apical microvilli
- Specialized for absorption of
nutrients and water

Interspersed with cells that have
glandular functions

  - Many of these secrete mucous (known as goblet cells)
 -  Mucous has a protective and a digestive role
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86
Q

the intestinal mucosa epithelial layer sits on a bed of
highly vascularized loose connective tissue known as the

A

lamina propria

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87
Q

Blood and lymphatic capillaries causes

A

absorption of nutrients and water
from across the epithelial cell into
blood

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88
Q

Immune cells are present in the inestinal mucosa
layer which functions as

A

protection from hostile microbes and tolerance to healthy microbes

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89
Q

in the intestinal mucosa the Layer of smooth muscle – the muscularis mucosa is important for

A

maintain the shape of the structure

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90
Q

Finger-like projection of epithelium
and lamina propria of the intestinal mucosa are called

A

the villus

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91
Q

Paracellular route

A

between adjacent
enterocytes - mostly regulated by tight
junctions

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92
Q

Transcellular route

A

through enterocytes,
across cell membranes – regulated by
membrane proteins

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93
Q

paracellular route of celiac disease

A

Gliadin binds to a protein (FYI – chemokine
receptor CXCR3)

signaling cascade that causes release of a
signalling protein called zonulin

Zonulin release leads to phosphorylation of
ZO proteins

disassembly of claudin and occludin proteins
at the tight junction

leakage of gliadin into the immune cell- containing lamina propria

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94
Q

what are the main functions of the skin

A
  • Protective barrier
    Mechanical, chemical or
    thermal injuries
  • Important barrier to
    infection
  • Reduces heat, fluid,
    electrolyte loss
  • Key for regulating body
    temperature
  • Provides sensory
    information
  • Limited importance in waste removal and vitamin synthesis (vitamin D)
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95
Q

what are the three layers of the skin

A
  • epidermis
  • dermis
  • subcutaneous
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96
Q

what are the varies of thickness of the skin

A

Thick – palms and soles
Epidermis is 0.4 – 1.4
mm thick
Thin – everywhere else
Epidermis is 0.075 – 0.15
mm

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97
Q

what are the epidermal layers from outermost to innermost

A
  • Stratum corneum
  • Stratum lucidum
    only in thick skin
  • Stratum granulosum
  • Stratum spinosum
  • Stratum basale
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98
Q

what are some characteristics of the stratum coreum

A

most superficial

layer size - 15-30 cell layers

most important component of the barrier
- prevents penetration of microbes
- prevents dehydration
- mechanical protection

skin cells in this layer are dead and full of keratin and filaggrin
- held together by tight juinctions, desmosomes
- filaggrin helps keratin aggregate into large macrofibrils

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99
Q

what are some characteristics of stratum lucidum

A

immediately below s corneum

  • only found in thick skin of the palms, soles and digits

3-5 cell layers

  • prtoection
  • cells are dead
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100
Q

Stratum Granulosum characteristics

A

between s corneum and s spinosum

3-5 cell layers compacted and flattened

living cells that are re organizing keritin and associating it with flaggrin and other protiens

when they die they release lamellar granules which are lipid rich and help reduce water loss

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101
Q

Stratum Spinosum characterisitics

A

superficial to the s.
basale

▪ 8-10 cell layers – in most skin this
is the thickest layer

▪ Very thick in thick skin

  • Very busy synthesizing keratin,
    proto-filaggrin, and other proteins
    ▪ Eventually keratin becomes 50%
    of the cell mass of keratinocytes
    ▪ Thick bundles of keratin called
    tonofibrils are linked to
    desmosomes
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102
Q

Stratum Basale function and characteristics

A

deepest epidermal layer

single layer

Stem cells divide and give rise to all of the layers

melanocytes

Wide range of sensory receptors

Resident immune cells

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103
Q

what are melanocytes

A

Synthesize and distribute
melanin to keratinocytes

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104
Q

describe the keratin structure

A

Fibrous protein – strong, often flexible long proteins that
have a relatively simple, repeating secondary structure

  • have many hydrophobic amino acid residues that are insoluble in water
105
Q

describe alpha keratin

A

alpha-helical protein with many levels of
structure:

Single “strand” protein arranged in an alpha helix

RIGHT HANDED COIL

106
Q

what is a coiled coil of an alpha keratin

A

two strands coiled around eachother

LEFT HANDED

The two strands interact with each other at sites of
hydrophobic amino acid residues

Rich in alanine, valine, leucine, isoleucine, methionine,
phenylalanine (all hydrophobic)

107
Q

what is a keratin Protofilament

A

long chains of two coiled coils

108
Q

what is a keratin Protofibril

A

two long chains of protofilaments

109
Q

what is hard keratin

A

just keratin with no fliaggrin or phospholipids
- hair and nails

110
Q

what are the dermal layers from outermost to innermost

A

papillary layer
reticular layer

111
Q

what are some characteristics of the papillary layer

A

superficial 1/5

interlocks dermis and epidermis
- papilla = “ fingers”
- dermal papillae are vascularized
- also contains sensory receptors

112
Q

what are some characteristics of the reticular layer

A

—– Usually thickest layer of the skin – thickest over the back
(4 mm)

houses:
- hair follicles
- nerves, arteries, veins and lymphatics
- sebaceous and sudoriferous sweat glands
- some adipose tissue
- smooth muscle cells
- some sensory receptors

113
Q

coiled coil of an alpha keratin is …….. handed

A

left

114
Q

alpha keratin is a …… handed coil

A

right

115
Q

what kind of CT is in the reticular layer

A

Dense irregular CT - type I collagen and elastic fibers

116
Q

what kind of CT is the papillary layer made out of

A

Loose CT
- fine elastic fibers, type 3 and type 1 collagen

117
Q

T or F dermal papillary layers are vascularized

A

T

118
Q

what are fibril forming collagens

A

Type 1,2 and 3

119
Q

type 1 collagen forms …. of the bodys collagen and has the most …..

A

90%

structural strength

120
Q

what cell in the dermis produces collagens

A

fibroblast

121
Q

where does assembly of the fibril forming collagens take place

A

extracellular space

122
Q

Collagen is a ………. structure but is not a ……

A

coiled coil

a helix

123
Q

what does a tropocollagen consist of

A

three collagen a chains are coiled around each-other

  • themselves are twisted, not coiled
124
Q

how is the tight twisting of the a-chains accomplished

A

unique amino acid structure

125
Q

Gly -X -Y often collagen fiber X is

A

proline but not always

126
Q

Gly -X -Y often collagen fiber Y is

A

hydroxyproline but not always

127
Q

Hydroxyproline and proline have rigid

A

“kinked”
structures

These provide the sharp “twists” or “kinks”
in the molecule

128
Q

Vitamin C is crucial to ………. and ……… of hydroxylated a.a.s

A

collagen formation

cross linking

129
Q

fibroblasts produce ……… that have some degree of hydroxylation of glycosylation that are secreted into the ECM

A

tropocollagen fibers

130
Q

outside of the cell, tropocollagen molecules are assembled into

A

fibrils and fibres

these fibers are also linked into proteoglycans and glycoprotiens

131
Q

what is a hair follicule?

A

An epidermal in-growth into the
dermis (invagination) that builds a
long structure formed from hard
keratin = a hair

All hair follicles, although found
in the dermis, are derived from
the epidermis

Specialized keratinocytes

132
Q

Are there areas of the skin completely
without hair?

A
  • Palms and soles
  • Lips, genital structures (glans penis,
    labia minora, clitoris)
133
Q

dermal papilla ……. the bulb supplying ….

A

contacts

capillary network

134
Q

keratinocytes at the papilla are very similar to the …… and spimosum

A

stratum granulosum

135
Q

what is the spinosum (hair matrix) useful for

A

active site of cell division

  • constantly going through mitosis
  • constantly growing upwards
136
Q

melanocytes in the blub transfer

A

melanosomes and keratinocytes

137
Q

what are the three layers of the hair shaft

A

medulla
cortex
cuticle

138
Q

medulla in the hair shaft is ………. the cortex is ……… in the cuticle the structure of ….. is more easily seen

A

lightly keratinized

filled with hard keratin

keratinocytes

139
Q

technically it is not called a hair shaft until it passes beyond the …

A

epidermis

140
Q

what is the arrector pilli

A

a bundle of smooth muscle cells that pull the shaft into a more erect position

  • innervated by the sympathetic nervous system, found on the same side as the sebaceous gland
141
Q

what determines if you have straight or curly hair

A

the shape of the cortex

142
Q

the hair root plexus has very …..

A

sensitive mechanoreceptors

  • myelinated nerves
  • desensitize rapidly
143
Q

why does the arrector pili pull the shaft into a more erect position

A

prevent us from loosing heat too quickly

doesnt let the cold in

144
Q

what are the three phases of hair growth

A

anagen
catagen
telogen

145
Q

anagen is a ………

A

longer period of mitotic activity and growth

146
Q

catagen arrested ……..

A

growth and regression of the hair bulb

147
Q

telogen is …….. often causing

A

cellular inactivity
hair shedding

148
Q

at the begining of the next anagen phase …………….

A

epidermal stem cells produce progenitors

149
Q

progenitors give rise to the …

A

matrix of the new hair bulb

150
Q

stem cells are located in the …… of the follicle, the external root sheath, near the attachement points of the arrector pilli

A

outer layer

151
Q

hyposermis / subscutaneous tissue and superficial fascia is the …….. contains ……. and is important in …………….. it is a ………… insulating against ……… The superficial region contains ……

A

Lower most layer

Contains loose areolar
and adipose tissue

Important in
stabilizing the position
of the skin in relation
to underlying tissues

Fat storage area,
insulates against
excessive heat loss

vessles

152
Q

what colours skin

A

Hemoglobin: red
blood cells in
vasculature below
epidermis

If deoxygenation
occurs (hypoxia)
then the skin looks
relatively “blue” -
cyanosis

153
Q

what is carotene

A

yellow
pigment from plants
in the diet

154
Q

what is melanin

A

pale yellow
to black pigment
produced by
melanocytes

155
Q

what do you call a flat lesion less than 5mm

A

macule

156
Q

what do you call a flat lesion larger than 5mm

A

patch

157
Q

what is a flat and raised lesion less than 5mm

A

papule

158
Q

what is a flat and raised lesion called that is larger than 5mm

A

plaque

159
Q

what is a solid bump with no fluid less than 5mm and more than 5mm

A

papule
nodule

160
Q

what os a serous fluid filled lesion less than 5mm and larger than 5mm

A

vesicle and a bulla(e)

161
Q

what is a puss filled lesion smaller than 5mm and larger than 5mm

A

pustule (cyst)
abbess or cyst

162
Q

what is a scale

A

accumulation or excess shedding of the stratum
corneum – can be dry or waxy-feeling.

163
Q

what is the result of defects in the moisture barrier (filaggrin) and tight junctions

A

antigens getting past the epidermal barrier over and over again

recruitment of immune cells

164
Q

atopic dermatitis is noted by

A

edema in the epidermis
the lymphocytes and mast cells
hyperkeratotic skin

165
Q

what is typically seen in psoriasis

A

epidermal hyper-proliferation and they divide very quickly

abnormal differentiation of epidermal keratinocytes

granulosa is absent
- enlarged blood vessels

166
Q

what is vitiligo

A

disorder of skin pigmentation

immune system attacks the cells that produce melanin

167
Q

what is alopecia areata

A

NK cells and cytotoxic T cells attack the hair follicle

patchy hair loss that does not scar and will re grow

168
Q

what is an absess

A

a pocket of purulent fluid (bigger than a pustule) – not lined by epithelium

169
Q

what is an ulcer

A

a defect in the epidermis, down at least to dermis level, usually due to impairment of healing/re-epithelialization

170
Q

vascular lesions description

A

include telangiectasias (dilated arterioles, venules that one can
see with the naked eye) and hemangiomas (many different
types of vessel-rich, red or violet growths)

171
Q

what is androgenetic alopecia

A
  • hair loss over the crown
    men posterior and lateral scalp
    women
    mid frontal hair loss
    vertex temporal regions spared: frontal hair line

gradual conversion of terminal hairs to vellus hairs - inherited

greatly dependent on androgen exposure over time in men

androgens may less responsible in women

often larger psychosocial impact on women

172
Q

what is acute telogen effluvium

A

non scarring alopecial characterized by acute / subacute diffuse hair shedding

metabolic or hormonal stress or by medications
- stressor causes anagen hair to enter telogen

recovery is spontaneous and occurs in 6 months

more chronic form also exists

173
Q

was is reversible cell injury

A

a cell/tissue has been released, but overcomes this stress and resumes normal physiologic function

174
Q

what is irreversible cell injury

A

a tissue/cell had beome damaged and will eventually die due to severity of the damage

175
Q

what are the major concepts of apoptosis

A

initiation
- apoptotic signals recognized
- initiator caspases

execution
- capases are activated by the initiator and cause cellular changes and apoptosis

176
Q

intristic apoptosis happens in the

A

mitochondrial pathway

177
Q

extrinsic apoptosis happens in the

A

death receptor pathway
- outside of the cell

178
Q

describe the extrinsic pathway

A

receptor ligand interactions (Fas and TNF receptor)

initiates caspases then exectioner capsases

179
Q

intristic pathway results from ……. or from lack of …. results from increased permeability of the ……… with consequent release of death inducing molecules into the cytoplasm

A

cellular damage
growth factors
mitochondrial outer membrane

180
Q

release of pro apoptotic protiens is highly controlled by the …….

A

BCL2 family of proteins

181
Q

Bcl2 , Bcl x and Mcl-1 are ….

A

anti apoptotic

because of high levels in the presence of growth factors and other signals that indicate a viable cell

182
Q

what is the role of anti apoptotic in prevention of apoptosis

A

keep the mitochondria from spilling out its guts
prevent mitochondrial pore formation and leakage of cytochrome c

183
Q

Bax and Bak are ….

A

pro apoptotic

184
Q

pro apoptotic can form …..

A

channels in the mitochondria and allow leakage

185
Q

where are Bax and Bak formed?

A

3 “BH” domains called BH1-3

186
Q

Bim, Bad , Bid, Puma and Noxa are increased when the cell is …… or should undergo …

A

stressed
apoptosis

187
Q

how main domains have the BH domain

A

only one called BH3

188
Q

what increases Bim, Bad , Bid, Puma and Noxa

A

ER stress
lack of growth signals
DNA damage

189
Q

what activates the mitochondrial leak channel (Bax/Bak)

A

lack of BH4 molecules
presence of BH3 only molecules

190
Q

what happens if you open the mitochondrial leak channel

A

cytochrome C leaks into cytosol
cytochrome C directly activates a protien known as apoptosis-activating factor (APAF) which causes an activation of caspases

191
Q

the anti apoptotic and pro apoptotic Bh families …………….

A

conteract eachother

the balance between the two will determine wether a cell will pursue apoptosis

192
Q

what would be seen in a viable cell

A

survival (growth) factor present
production of anti apoptotic proteins present
BCL2 is being transported into the mitochondria
Cytochrome C is withheld in the mitochondria and there is no leakage

193
Q

what would be found in an apoptotic cell

A

lack of survival signals
irrigation/ DNA damage

causing an activation of sensors BH3 only proteins

antagonism of BCL2

activation of BAX/BAK channel

leakage of cytochrome c

activation of caspases

apoptosis

194
Q

apoptosis activating factor

A

stimulus cytochrome C

forming pores and releasing cytochrome C

Apaf1 associates with cytochrome C

assembly of an apoptosome (multiple units of a cytochrome C with Apaf1)

recruitment of caspase 9

activation of caspase 9 cleaves and activates exicution caspases

195
Q

what are the key executioner caspases

A

3,6

9 is cleaved to activate them

196
Q

initiated by activation of the plasma membrane death receptors on a variety of cells

A

extrinsic pathway

197
Q

intracellular death domains of the extrinsic pathway

A

activate caspases 8 and 10

198
Q

caspases 8 and 10 then activate

A

other caspases that are involved in the execution phase

199
Q

Fas is a …

A

death receptor

200
Q

FasL is expressed on

A

immune T cells that recognise self antigens and some cytotoxic T cells

201
Q

when FasL binds to Fas they form …

A

a binding site called Fas- associated death domain (FADD) which activates caspases 8 and 10

202
Q

both intrinsic and extrinsic pathways

A

converse in execution phase

203
Q

caspases 8,9,10 can alla ctivate executioner caspases such as

A

3 and 6

204
Q

executioner caspases can

A

cleavage of DNA
destroy nuclear matrix
destroy cytoskeletal changes
activated flipases

205
Q

what is the end result of the execution phase

A

DNA is cut into discerete lengths by endonucleases activated by caspases

206
Q

phosphitidylserine … to the outer membrane

A

flips

allows macrophages to recognize and phagocytose

207
Q

apoptoic pathways growht factods increase the synthesis od

A

Bcl-2 and Bclx

208
Q

dna damage leads to the synthesis of….

A

p53

p53 stimulates Bax/Bak

209
Q

misfolded proteins that accumulate in the ER cause ER stress which causes …

A

production of caspases

210
Q

with protein misfolding is very stressful for the ER ….

A

too much demand, beyond capacity

211
Q

chaperone proteins are …

A

ATP dependant

212
Q

Necroptosis resembles necrosis but unlike necrosis

A

loose ATP
cell swelling
generation of free radicals
does not involve caspases activation

it is triggered by genetically programmed signal transduction

213
Q

what is the mechanism of action for necroptosis

A

similar to extrinsic pathway binding of ligand to receptor

TNF tumor necrosis
RIP

214
Q

hypertrophy is an increase

A

of cells which increase organ size

ex heart

215
Q

what is hyperplasia

A

increase in the number of the cells in an organ

risk factor long term for malignancies

216
Q

Atrophy is

A

a decrease in the numer or size of cells

loss of blood supply/ nerve supply

217
Q

what are the three types of autophagy

A

chaperone mediated lyposomal digestion
macro autopahgy

218
Q

what causes autophagy

A

cellular stresses such as nutrient depreviation activates autophagy through

initation
nucleation
elongation of isolation

219
Q

where are autophagosome phagopores derived from?

A

the ER

220
Q

phagopores are influenced by

A

initation and nucleating complex

causes it to surrond cellular components

221
Q

autophagosome docks with

A

lysosome

222
Q

what is pathogenic calcification

A

abnormal tissue deposition of calcium salts

223
Q

what are the two forms of calcification

A

dystrophic
metastatic

224
Q

what is dystrophic calsification

A

in dying tissue
usually present in atherosclerotic plaques

appear as macroscopically as fine white granules or clumps

225
Q

in dystrophic calcification calcium is concentrated in ……… in cells by a process that is initiated by …….

A

membrane bound vesicles

membrane damge

226
Q

what are the steps of dystrophic calcification

A
  1. calcium ion binds to the phospholipids present in the vesicle membrane
  2. phosphatases associated with the membrane generate phosphate groups which bind to the calcium
  3. the cycle of calcium and phosphate binding is repeated, raising the local concentration and producing a deposit near the membrane
  4. a microcrystal is formed which can lead to propagate and more calcium deposition
227
Q

metastsic calcification

A

occurs in normal tissues due to diseases increases serum lelves

tends to affect intersitiual tisses of the gastic mucosa

tissues secrete acid at the surface of the cell

on the opposite surface, the cell is more alkaline

calcium precipitates in a more alkaline environment

228
Q

what are the morphalogic patterns of necrosis (the 4 types)

A
  1. coagulative
  2. liquefactive
  3. caseous
  4. fat necrosis
229
Q

what is coagulative necrosis

A

preservation of the basic outline of the coagulated cells

GHOST cells, no nuclei

effected tissue is firm
- most solid organs

230
Q

nerotic cells are eventually removed by

A

fragmentation and phagocytosis of cellular debris

231
Q

liquefactive neurois is

A

characterized by focal bacteria or funcgal infections acumulate inflammatory cells

completely digests dead cells

liquid viscous mass

232
Q

caseous necrosis is

A

distinctive form of coagulative necrosis

cheesy in appearance

found often in TB infections (lung)

entire structure is known as gramuloma

no cell boarders - imflammatory border

233
Q

fat necrosis is

A

not a specific pattern
- refers to a focal area of fat destruction

typically occurs as a result of release of activated pancreatic lipases into the pancreas and the peritonal cavity

visible chalky white areas

234
Q

most necrotic cells and debris disappear with

A

combination of enzymatic digestion and fragmenation, followed by phagocytosis of debris by leukocytes

if not destroed and reabosrbed tend to atract calcium salts

235
Q

types of insults to the cell or tissues

A

hypoxia and ischemia
infection, inflammation and immune mediated disorders
- toxins / chemical agents
- trauma , compression and thermal injuries
- deficiencies in nutrients or growth factors

236
Q

the cellular response injury depends on

A

type of injury
duration of injury
severity of injury
the adaptability and metabolism/phenotype of the cell

237
Q

what are some reverisble cell injuries

A
  • cellular swelling
  • non specific nuclear changes
  • ribosomal detachment, membrane abnormalities die to cytoskeletal dissasembly, accumulation of lipids
  • lipid vaculoles inlarge, collection of damaged membranous components
  • loss of mRNA
  • small bubble like outpouchings in the membrane
238
Q

what are some reversible injuries that can not be seen

A

changes in calcium concentrations

unfolded proteins

damage to DNA or cytoskeletal elements

loss of membrane potentials or abnormal distribution of molecules across the cell membrane

ATP depletion

239
Q

karolysis is

A

chromatin fades

240
Q

pyknosis

A

chromatin condenses more basophillic, nucleous shrinks

241
Q

karyorrhexis

A

nucleus fragments

242
Q

necrosis is

A

the injured cell immediate loss of cellular viability

243
Q

what can necrosis be caused by

A

depletion of ATP
mito damage
calcium accumulation
oxidative stress/free radicals
membrane damage
denatured proteins
DNA damage

244
Q

how does ATP depletion cause cell injury

A

dysfunction and swelling of the sodium potassium pump

anaerobic metabolism decreases pH

increases production of free radicals

failure of calcium pumps

reduction in protein synthesis, detachment of ribosomes causing misfolding of proteins

245
Q

calcium accumlation in the cell

A

activate variety of destructive enzymes

directly activate caspases

cause calcium release - decreased ATP

246
Q

why is calcium a special ion

A

only ion that is ubiquitous second messanger

interacts with alot of intracellular proteins

247
Q

mitochondrial damage

A

membranes can be damaged by free radical attack

cytosolic calcium increase too high in the cell MPTP can open
- loss of mitochondrial membrane potential
- releases H+
- further increase in cytoplasmic calcium

inability to generate ATP and ultimately necrosis

248
Q

lipid breakdown can result in

A

leaky membranes
lipid breakdown

detergent like effects
- unesterfied free fatty acids
- acyl carnitine
- lysophospholipids

249
Q

cytoskeletal abnormalities

A

activation of protases by increased cytosolic calcium

250
Q

injury to lysosomes membranes results in

A

direct enzymatic damage by lysosomal enzymes
activation of enzymes by lysosomal enzymes

251
Q

how are free radicals generated

A

normal metabolic processes

metabolism of drugs or toxins

radiation

fenton reaction - metals recieve or donate electrons

leukocytes

252
Q

how is superoxide formed eliminated and what are the pathogenic effects

A

formed
- incomplete reduction of O2 during oxidative phosphorylation by phagocte oxidase in leukocytes

eliminated
conversion of H2O2 and O2 by SOD

pathogenic effects
production of degratative enzymes in leukocytes and other cells; may directly damage lipids , proteins and DNA

253
Q

how is hydrogen peroxide formed, eliminated and what are the pathologic effects

A

formed
generated by SOD from O2 and by oxidases in peroxisomes

eliminated
conversion of H2O and O2 by catalase

pathologic
can be converted to OH and OCL which destroy microbes and cells

254
Q

how id hydroxyl OH- formed, eliminated and what are the pathological effects

A

formed
generated from h20 by hydrolysis

eliminated
conversion to water by glutathione peroxidase

pathologic
most reactive oxygen derived free radical ; principle ROS responsible for damaging lipids, proteins and DNA

255
Q

peroxynitrite formation, elimination and patholgic effects

A

formed
generated by O2 and NO synthase in many cell types

elimination
conversion to HNO2

pathologic
damages lipids , proteins and DNA

256
Q

what is the fenton reaction

A

oxidation process activated by Fe(II) salts in the presence of H2O2 that generates radical species in solution and oxidizes a wide range of organic substrates with high activity but generally poor selectivity.

257
Q

what are some mechanisms to remove free radicals

A

antioxidants
enzymes

258
Q

if you black protein synthesis …. is blocked

A

apoptosis

259
Q

what are some causes of apoptosis

A

programmed destruction
hormone dependant involution
cell deletion in proliferating cell populations

Biomed (9 decks)

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